Derivatives of 2, 7-diaminothioxanthone dioxide



Patented Aug. 18, 1953 UNITED STA ATENT OFFICE DERIVATTVES OF 2,7-DIAMINOTHIOXAN- THONE DIOXIDE v N Drawing. Original application July 23', 1946;

Divided and this application December 6, 1950, Serial No. 199,586

Serial No. 685,787.

i Claims.

The present invention relates to new chemical compounds and more particularly to aldehyde sulfoxylate and aldehyde bisulfite derivatives of 2,7-diaminothioxanthone dioxide and 2,7-diaminothioxanthenol dioxide. These compounds characterized by aldehyde sulfoxylate and bisulfite substituted aminophenyl group-s linked together by a carbonyl or hydroxy-methylene group and the sulfone (S02) group are of value for combating bacterial infections.

The compounds may be represented by the following formula:

where X is selected from the group consisting of carbonyl and hydroxymethylene, and R is selected from the group consisting of aldehyde sulfoxylate and bisulfite radicals.

EXAMPLE I 2,7-diaminothiomanthone dioxide This compound is conveniently prepared in a four-step process as follows:

(a) 5-nitro-2-(p-mitrothiophenoxy) benadldehyde.-A hot solution of 5-nitro-2-chlorobenzaldehyde (0.14 mole) and 350 ml. of alcohol is prepared and diluted with 140 ml. of Warm water. p-Nitro-thiophenoxide (0.15 mole) is then added with stirring. The mixture is heated to reflux for about 1 hour, and after cooling the precipitate is filtered and washed successively with cold alcohol and water. The yield of 5-nitro-2-(p-nitrothiophenoxy) benzaldehyde is high.

(b) Cyclization of 5-m'tro-2-(yp-nitrothiophenosey) benzaZdeh' de.The dry product obtained in step (a) (0.12 mole) is added with stirring to concentrated sulfuric acid (370 ml.) over a period of about 1 hour. The mixture is slowly heated to 60 C. and is maintained at this temperature for 15 mins, whereupon it is cooled and poured onto chipped ice (about 600 grams). The precipitate which separates is filtered, washed with water, and dried. The product is a mixture of 2,7-dinitrothioxanthone and 2,7-dinitrothioxanthone, which is not separated.

(c) 2,7-dinitrothioccanthone dioride.The dry product from step (b) is heated to reflux with a mixture of glacial acetic acid (730 ml.) and 30% hydrogen peroxide (103 grams) for 4 hours. The reaction mixture is cooled and the precipitate is filtered and washed successively with water, sodium bicarbonate solution, and again with 2. water. The yield of dry 2,7-dinitrothioxanthone dioxide is high.

(d) 2,7-diaminothioxantho ne diomide.A suspension of 2.,7-dinitrothioxanthone dioxide (0.1 mole) in glacial acetic acid ml.) is prepared and is heated to 80"' on a steam bath. A solution of stannous chloride dihydrate (0.75 mole) in glacial acetic acid (450 ml.) saturated with gaseous hydrogen chloride is added gradually with stirring. After the addition of all the stannous chloride, heating is continued for about 2 hours at 80 C. The mixture is now cooled to 10 C. and the precipitate is removed by filtration and washed thoroughly with Water. The Washed filter cake is suspended in water made alkaline by the addition of sodium hydroxide solution, and the orange colored diami'no compound is then filtered with suction, washed with water and dried. The crude product is heated to reflux with about 500 ml. of acetone. The hot mixture is filtered and. the clear yellow filtrate concentrated to a volume of about ml. Upon cooling the pure 2,7-diamino-thioxanthone dioxide, M. P. 293.5-298 C., separates as a yellow crystalline powder in good yield.

EXAMPLE II 2,7-.diaminothio=xdnthenol dioxide 2,7-dinitrothioxanthone dioxide (0.1 mole) in 80% acetic acid (400 m1.) is heated gradually to reflux with zinc dust (1.0 equivalent) which has previously been Washed with hot dilute hydrochloric acid. The initial phase of the reduction is spontaneously exothermic and external heat is not required. The total reflux period is about 1 hour with the liquid becoming a pale yellow in color. The boiling mixture is then filtered to remove the excess zinc and the hot filtrate is diluted with 1500 ml. of hot water. On cooling, a colorless precipitate separates which is suction filtered, and Washed with sodium bicarbonate solution followed by water. The yield of dry product, M. P. 204 C., is high. After recrystallization (Darco) from about 400 ml. of alcohol, the product melts at 212 C. with decomposition.

The derivatives to which the present application is directed are prepared by reacting the products of Examples I and. II with aldehyde sulfoxylate and aldehyde bisulfite products. The following examples are illustrative:

EXAMPLE III Sodium 2,7-diaminothioxcmthdne dioxide bisformaldehydesulfomylate dihydrate 2,7-diaminothioxanthone dioxide (0.044 mole) is heated for 6 hours in a mixture composed of 3 23 ml. of 99.5% methanol, 455 ml. of absolute alcohol and sodium formaldehyde sulfoxylate dihydrate (0.088,mole) which has been recrystallized from water. After cooling, the precipitate is removed by filtration and washed with acetone until a sample of the product forms a clear, aqueous solution. The material is dried in vacuo over phosphoric anhydride. The yield of sodium 2,7- diaminothioxanthone dioxide bisformaldehyde sulfoxylate dihydrate, M. P. 279 C. with decomposition, is high. 7

EXAMPLE IV S odiwm 2,7 -dz'a.min othiozmnthone dioxide-MN- bz's- (3-phenyZ-2 -prope ne-1 -sulfonate) This is the sodium cinnamaldehydebisulfite derivative of 2,7-diaminothioxanthone dioxide. A mixture of 2,7-diaminothioxanthone dioxide (0.0036 mole) and sodium cinnamaldehyde bisulfite (0.0068 mole) is heated to reflux in 60 ml. of absolute alcohol for about 7 hours. After cooling, the product is removed by filtration and washed three times with acetone to yield a pale yellow powder which is completely soluble in water. The melting point is 256.5-265.5 C. with decomposition.

EXAMPLE V Sodium 2,7-diaminothioxanthenol dioxide bisformaldehydesulfoxylate 2,7 -diaminothioxanthenol dioxide (0.054 mole) and recrystallized sodium formaldehydesulfoxylate (0.106 mole) are refluxed in a mixture of 99.5% methanol (30 ml.) and absolute alcohol (600 ml.) on a steam bath for 4 hours. After cooling, the colorless precipitate is removed by filtration, Washed with ether and dried in vacuo over phosphoric anhydride. The yield of sodium 2,7-diaminothioxanthene dioxide bis-formaldehydesulfoxylate is 7 high. This, product melts at 269 C. with decomposition.

The present application is a division of my prior application Serial No. 685,787 filed July I claim: ,7 1. A compound represented by the following formula:

RHN /X\ NHR where X is selected from the group consisting of carbonyl and hydroxymethylene, and R is selected from the group consisting of aldehyde sulfoxylate and aldehyde bisulfite radicals, wherein the aldehyde portion of the radicals is selected from the group consisting of formaldehyde and cinnamaldehyde and wherein R. is attached to the respective amino groups through its reactive aldehyde carbon atom.

2. Sodium 2,7-diaminothioxanthone bisformaldehydesulfoxylate.

3. Sodium 2,7-diaminothioxanthenol dioxide bisformaldehydesulfoxylate.

4. Sodium 2,7-diaminothioxanthone dioxide- N,N'-bis- (3-phenyl-2-propene-1 -sulfonate) EDWARD DELBERT AMSTUTZ.

dioxide Country Date Germany Sept. 2, 1935 Number 

1. A COMPOUNDS REPRESENTED BY THE FOLLOWING FORMULA: 